Pancreatitis is a painful condition that may become recurrent or chronic in genetically susceptible individuals. Patients with pancreatitis suffer multiple hospital admissions, pain episodes, addiction to pain medications, and psychosocial stressors by missing school by the child and work by family members. As an important underlying etiology of pancreatitis, genetic factors are becoming an integral component of diagnostic algorithms. In order to translate recent advances into opportunities to improve clinical care, we propose to develop a high- throughput gene chip that identifies mutations in the genes that cause the most common forms of inherited syndromes of pancreatitis. In this Phase I application, we will test the technical merit of a gene sequencing platform that is customized to patients with pancreatitis, which we call the PancreasCHIP. Our Specific Aim in this Phase I application is to determine the accuracy of the PancreasCHIP to sequence the target genes. We will pursue this aim by testing two hypotheses. First, we hypothesize that the PancreasCHIP sequences the target genes at >99% accuracy. In preliminary studies, we analyzed the nucleotide composition of the 6 target genes and designed a one-step TruSeq multiplex platform to generate amplicons for all exons and target intron-exon boundaries, with >99% coverage. We will generate amplicons in healthy subjects (serving as controls) and compare chip readouts with known sequences. Second, we hypothesize that the PancreasCHIP identifies mutations in patients with pancreatitis. To this end, we will examine whether the sequence output produced by the PancreasCHIP detects insertions, deletions, or indels in DNA of patients with chronic (familial) pancreatitis. Collectively, these experiments will validate the technical merits of PancreasCHIP, and will position us for future experiments to further bench-test the assay and develop an automated detection algorithm in a future Phase-II application. Ultimately, our goal is to bring the customized sequencing platform to full use in the clinic to readily facilitate diagnostics and personalized care of patients with pancreatic diseases.